Polysaccharide Utilization in Human Gut Microbiota

The human gut microbiota comprises a vast consortium of bacteria that harvest energy from dietary and host-derived polysaccharides indigestible by human enzymes. Central to this process are specialised gene clusters known as polysaccharide utilization loci (PULs), which encode carbohydrate-active enzymes (CAZymes), transporters and surface-exposed binding proteins. These systems enable bacteria to recognise, deconstruct and import complex glycans ranging from plant cell wall polymers to mucin O-glycans. Degradation products such as short-chain fatty acids promote gut health, modulate immune function and influence host metabolism. Distinct bacterial phyla deploy varied strategies: Bacteroidetes rely heavily on Sus-like systems and TonB-dependent transporters, while Firmicutes often organise CAZymes into Gram-positive PULs. Co-operative and competitive interactions for shared breakdown products shape community structure, with keystone degraders orchestrating cross-feeding networks. Advances in multi-omic profiling reveal dynamic transcriptional responses to dietary shifts and uncover regulatory small RNAs that fine-tune polysaccharide foraging. A deeper mechanistic understanding of these pathways holds promise for precision modulation of the microbiota through targeted dietary fibres or enzyme inhibitors, with applications in metabolic disease, inflammatory disorders and beyond.

Research from Nature Portfolio

Recent studies have expanded our view of regulatory networks controlling polysaccharide foraging. In one investigation, an in vivo-relevant transcriptome atlas of Bacteroides thetaiotaomicron revealed dozens of small RNAs that respond to specific carbon sources and stress conditions. One such regulatory RNA was shown to attenuate antibiotic tolerance, linking nutrient sensing to antimicrobial susceptibility. Another study elucidated how Bacteroides species assemble TonB-dependent transporters with surface lipoprotein “lids” to capture vitamin B12 with high affinity. Structural and biochemical analyses demonstrated a pedal-bin mechanism in which lid closure triggers vitamin release and subsequent import, highlighting lipoprotein-assisted uptake as a general strategy for critical micronutrients. Together, these findings underscore the intricate coupling between glycan and vitamin acquisition systems and the regulatory circuits that optimise resource utilisation in the gut environment.

Polysaccharide Utilization in Human Gut Microbiota publication trend

The graph below shows the total number of articles in polysaccharide utilization in human gut microbiota across all publications each year (not limited to Nature Index journals).

Technical terms

Polysaccharide Utilization Loci (PULs): Gene clusters encoding sensor proteins, binding modules, transporters and enzymes for targeted degradation and uptake of complex carbohydrates.

Carbohydrate-Active Enzymes (CAZymes): A diverse group of enzymes that catalyse the assembly and breakdown of glycosidic bonds in polysaccharides.

Sus-like systems: Surface-anchored membrane complexes first characterised in Bacteroides for starch binding and degradation, now recognised for broad glycan utilisation.

TonB-dependent transporters: Outer-membrane proteins that harness the TonB energy transduction system to import nutrients such as polysaccharide fragments and vitamins.

Small RNAs (sRNAs): Non-coding regulatory RNAs in bacteria that modulate gene expression in response to environmental cues, including nutrient availability.

References

1. An expanded transcriptome atlas for Bacteroides thetaiotaomicron reveals a small RNA that modulates tetracycline sensitivity. Nature Microbiology (2024).
2. BtuB TonB-dependent transporters and BtuG surface lipoproteins form stable complexes for vitamin B12 uptake in gut Bacteroides. Nature Communications (2023).
3. Architecture, Function, Regulation, and Evolution of α‑Glucans Metabolic Enzymes in Prokaryotes. Chemical Reviews (2024).
4. Recognition and Degradation of Plant Cell Wall Polysaccharides by Two Human Gut Symbionts. PLOS Biology (2011).
5. Glycan complexity dictates microbial resource allocation in the large intestine. Nature Communications (2015).